PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

Long-Term Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis Refractory to Biologic Therapies: 2-Year Results from the Phase 3 Select-Psa 2 Study

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.

Screening for asymptomatic deep vein thrombosis in COVID-19 patients admitted to the medical ward: a cross-sectional study.

PURPOSE: Patients with COVID-19 have an increased risk for venous thrombo-embolism (VTE), especially pulmonary embolism. The exact prevalence of asymptomatic DVT is not known, as is the usefulness of screening for DVT in patients admitted to ward with COVID-19. We have studied the prevalence of asymptomatic DVT. METHODS: We performed a cross-sectional observational multi-center study at four university medical centers in The Netherlands. All adult patients admitted with COVID-19 to a medical ward were eligible for inclusion, including patients who were transferred back from the ICU to the ward. The study protocol consisted of weekly cross-sectional rounds of compression ultrasound. RESULTS: In total, 125 patients were included in the study. A significant proportion of patients (N = 34 (27%)) had developed a VTE during their admission for COVID-19 before the study ultrasound was performed. In most VTE cases (N = 27 (79%)) this concerned pulmonary embolism. A new asymptomatic DVT was found in 5 of 125 patients (4.0%; 95% CI 1.3-9.1%) (Table 2). Nine patients (7.2%; 95% CI 3.3-13.2%) developed a VTE (all PE) diagnosed within 28 days after the screening US was performed. CONCLUSION: We have shown a low prevalence (4%) of newly discovered asymptomatic DVT outside the ICU-setting in COVID-19 patients. Despite this low prevalence, nine patients developed PE (7%) within 28 days after ultrasound. This favors the hypothesis of local thrombus formation in the lungs. Based on our findings and literature, we do not recommend US-screening of asymptomatic patients with COVID-19 admitted to the ward.

Efficacité et tolérance à long terme de l'upadacitinib chez les patients présentant un rhumatisme psoriasique réfractaire aux traitements biologiques : résultats à 2 ans de l'étude de phase III SELECT-PsA 2

L'upadacitinib (UPA), un inhibiteur de Janus kinase (JAK) par voie orale, a démontré son efficacité et sa sécurité chez des patients atteints de rhumatisme psoriasique (RP) ayant une réponse insuffisante ou une intolérance à ≥ 1 traitement de fond biologique (bDMARD) à la S56 de l'étude de phase III SELECT-PsA 2. Évaluer l'efficacité et la tolérance de l'UPA à S104 de l'extension à long terme en cours de l'étude SELECT-PsA 2. Patients randomisés pour recevoir UPA 15 mg, UPA 30 mg ou placebo (PBO) pendant 24 semaines. Les patients sous PBO passaient ensuite à UPA15 ou UPA30. Évaluation d'efficacité à S104 des patients traités en continu par UPA en NRI (imputation en non-répondeurs) et données observées (critères binaires), ou en MMRM (modèle mixte pour mesures répétées) et données observées (critères continus). Au total, 641 patients ont reçu ≥ 1 dose d'UPA. À S104, 38,4 % de l'ensemble des patients avaient arrêté leur traitement par UPA et les taux d'arrêt les plus élevés ont été observés chez les patients randomisés dans le groupe PBO à l'inclusion (total PBO : 46,7 %). Les motifs les plus fréquents d'arrêt du traitement étaient un manque d'efficacité (UPA15 : 12,3 %, UPA30 : 8,7 %, total PBO : 21,7 %) et la survenue d'un EI (UPA15 : 10,9 %, UPA30 : 13,3 %, total PBO : 12,7 %). La proportion de patients sous UPA ayant obtenu une réponse ACR20/50/70, MDA, PASI75/90/100, et résolution des dactylites/enthésites était similaire voire améliorée à S104 de traitement versus S56 (Tableau 1). La variation moyenne par rapport à l'inclusion du HAQ-DI, de l'évaluation de la douleur par le patient et des scores BASDAI/ASDAS était plus importante avec UPA. À S104, les réponses cliniques étaient similaires sous UPA15 et UPA30. Les données de tolérance à S104 (Fig. 1) concordaient avec celles rapportées à S56. Les infections graves, zonas, affections hépatiques, anémies, neutropénies, lymphopénies et élévations des CPK restaient plus élevés sous UPA30 vs UPA15. Les taux de cancers, d'EICM et de TEV étaient similaires dans les 2 groupes UPA. 1 décès rapporté avec UPA15 (inexpliqué, manque d'informations ;la patiente ayant récemment reçu un diagnostic de cancer de l'ovaire) et 2 avec l'UPA30 (pancytopénie et pneumonie à COVID-19). Chez les patients atteints de RP ayant présenté une réponse insuffisante ou une intolérance à ≥ 1 bDMARD, les réponses cliniques se sont maintenues avec UPA15 et UPA30 jusqu'à 2 ans de traitement. Aucun nouveau signal de sécurité n'a été identifié durant cette période d'extension. (French) [ FROM AUTHOR]

Efficacité d'upadacitinib chez des patients atteints de spondyloarthrite axiale non radiographique en fonction des signes objectifs d'inflammation à l'inclusion

L'essai de phase 3 SELECT-AXIS 2 (NCT04169373) a évalué l'efficacité et la tolérance d'upadacitinib (UPA) chez des patients atteints de spondyloarthrite axiale non radiographique (nr-axSpA). Nous présentons ici une analyse en sous-groupes (ss-gpes) en fonction de la valeur de la hsCRP et de l'inflammation des sacro-iliaques (SI) à l'IRM à la sélection. Dans SELECT-AXIS 2 [1] , des patients de ≥ 18 ans ayant un diagnostic clinique de nr-axSpA remplissant les critères de classification de 2009 de l'ASAS, mais sans le critère radiologique des critères de New-York modifiés, et présentant des signes objectifs d'inflammation active à l'IRM selon la définition de l'ASAS (évaluation par 2 lecteurs et un arbitre) et/ou un taux de hsCRP supérieur à la limite supérieure de la normale (LSN, 2,87 mg/L) à la sélection, ont été randomisés selon un ratio 1/1 pour recevoir UPA 15 mg 1x/j ou un placebo (PBO). Le critère principal était la réponse ASAS40 à la semaine (S) 14. Les autres critères incluaient la faible activité de la maladie (LDA) selon l'ASDAS (≤ 2,1), la variation par rapport à l'inclusion du SPARCC-IRM articulations SI, du BASFI et de la douleur rachidienne évaluée par le patient, à S14. Les analyses en ss-gpes préspécifiées (ASAS40) et post-hoc (autres critères) ont été réalisées en fonction du statut inflammatoire à la sélection : taux de hsCRP (> LSN vs ≤ LSN) et inflammation des articulations SI à l'IRM (positive vs négative). L'imputation des non-répondeurs (NRI) avec imputation multiple (MI) pour prendre en compte des données manquantes liées au COVID-19, a été utilisée pour les variables binaires. Un modèle mixte pour mesures répétées sur les données observées (AO) a été utilisé pour les variables continues sauf pour le score SPARCC-IRM pour lequel une analyse de covariance sur les AO a été utilisée. Sur les 312 patients inclus dans l'analyse, 176 (56 %) avaient une hsCRP > LSN et une IRM négative (IRM−), 73 (23 %) une hsCRP > LSN et une IRM positive (IRM+) et 63 (20 %) une hsCRP ≤ LSN et une IRM+. Les caractéristiques démographiques et cliniques à l'inclusion étaient similaires dans les ss-gpes ;cependant, le ss-gpe hsCRP > LSN et IRM+ était plus fréquent chez les patients HLA-B27 positifs et avait un plus faible taux de traitement antérieur par DMARDs biologiques (Tableau 1). À S14, des taux plus élevés de réponse ASAS40 et ASDAS-LDA et une réduction plus importante par rapport à l'inclusion des scores SPARCC-IRM, BASFI et de douleur rachidienne ont été associés à UPA vs PBO pour tous les ss-gpes (Fig. 1). La différence UPA vs PBO était plus importante pour le groupe hsCRP > LSN et IRM+, pour tous les critères. Dans SELECT-AXIS 2, les résultats chez les patients atteints de nr-axSpA ont été améliorés pour UPA versus le PBO pour tous les sous-groupes d'inflammation à l'inclusion ;le bénéfice le plus important a été observé chez les patients ayant à la fois un taux élevé de CRP et des signes d'inflammation à l'IRM à la sélection. (French) [ FROM AUTHOR]

LONG-TERM EFFICACY and SAFETY of UPADACITINIB in PATIENTS with PSORIATIC ARTHRITIS REFRACTORY to BIOLOGIC THERAPIES: 2-YEAR RESULTS from the PHASE 3 SELECT-PSA 2 STUDY

Background: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheu-matic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1 Objectives: To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods: Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results: A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion: In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identifed in this long-term extension.

HPV prevention and control - The way forward.

The global confrontation with COVID-19 has not only diverted current healthcare resources to deal with the infection but has also resulted in increased resources in the areas of testing and screening, as well as educating most of the global public of the benefits of vaccination. When the COVID-19 pandemic eventually recedes, the opportunity must not be missed to ensure that these newly created resources are maintained and redeployed for use in testing and immunisation against other vaccine-preventable infectious diseases. A notable example is infection by human papillomavirus (HPV), the commonest sexually transmitted human virus and the leading cause of a variety of cancers in both men and women, such as cervical, head and neck, anal, vaginal, vulvar and penile cancers. The most important is cervical cancer, the objective of the global elimination goals targeting the vaccination of young female and male adolescents, screening all women and treatment of all infected women. As the campaigns to control SARS-CoV-2, the eradication of HPV-induced cancers also relies on effective prevention and control programs. The lessons learned and the technical, logistical and human resources which have been established to combat COVID-19 by vaccination and testing must be applied to the eradication of other infections which affect the global population. This commentary summarizes the opportunities that the COVID-19 pandemic has created for HPV prevention and control, lists the already available tools for HPV control, and emphasizes the potential public health threats amidst the ongoing COVID-19 pandemic.

Comparison between myocardial function assessed by echocardiography during hospitalization for COVID-19 and at 4 months follow-up.

In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up. Of the 51 patients included at baseline, 40 (age: 62 years (IQR; 54-68), 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction (60% vs. 58%, p = 0.54) and tricuspid annular plane systolic excursion (23 vs 22 mm, p = 0.18) were comparable between hospitalization and follow-up, but a significantly lower RV diameter (39 vs. 34 mm, p = 0.002) and trend towards better global longitudinal strain (GLS) (- 18.5% vs - 19.1%, p = 0.07) was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.

TIPICO XI: report of the first series and podcast on infectious diseases and vaccines (aTIPICO).

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts.

Effect of dexamethasone on direct oral anticoagulant plasma levels in patients with COVID-19

Background : Dexamethasone is part of the standard treatment of COVID-19 patients who need oxygen support. COVID-19 patients have a high risk of venous and arterial thrombosis, therefore adequate anticoagulation is of vital importance. Direct oral anticoagulants (DOACs) are generally not recommended in patients with dexamethasone due to possible drug-drug interactions which may decrease DOACs plasma levels. Therefore, data on the interaction between dexamethasone and DOACs is urgently needed. Aims : To assess DOAC plasma levels in patients with simoultaneous use of dexamethasone. Methods : Trough and peak DOAC plasma levels, by means of antiactivated factor X (anti-Xa) were prospectively collected in hospitalized COVID-19 patients treated with dexamethasone and DOACs (apixaban, rivaroxaban and edoxaban) and in hospitalized COVID-19 patients treated with DOACs only, to assess whether these values were within reference range. Results : Data were collected across two centres in Italy and the Netherlands. A total of 20 patients, 16 with DOACs and dexamethasone and 4 with DOACs only were enrolled. Twelve patients were on anticoagulant treatment for atrial fibrillation, seven for venous thromboembolism, and one for myocardial infarction. In 15 patients DOACs were started during the hospitalization. None of the patients had trough DOAC plasma levels below reference range. Only one patient (6.3%) treated with rivaroxaban had peak levels below reference range. Six patients (37.5%) in the dexamethasone group and two control patients (50%) had peak or trough DOAC plasma levels above reference range. Conclusions : In COVID-19 patients, the effect of dexamethasone use on DOAC plasma levels seems limited. This suggests that DOACs can be safely started or continued in COVID-19 patients treated with dexamethasone.

[Lung ultrasound in patients with symptoms of covid-19]

The SARS-CoV-2 pandemic presents a challenge for healthcare worldwide. In this context, rapid, correct diagnosis and early isolation of infected persons is of great importance. Pneumonia as an expression of COVID-19 is responsible for the most part of morbidity and mortality. Lung ultrasound can provide valuable information about the diagnosis of a COVID-19 pneumonia in daily practice. A normal ultrasound excludes COVID-19 pneumonia. Conversely, finding abnormalities matching with a COVID-19 pneumonia can be useful for isolation policy. Follow up lung ultrasound visualizes the development of the pneumonia and a possible alternative diagnosis can thereby be determined in the event of a deviating clinical course.

Encouraging outcomes of solid organ recipients with covid-19

Introduction: Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Methods: Seven transplanted patients (two liver, three kidney, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. Transplanted patients admitted to the ICU were compared to immunocompetent patients admitted to the ICU (n=19). Results: The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18 and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours after admission. Weaning could be initiated in these patients after 16 and 19 days of mechanical ventilation, respectively. One kidney and the lung transplant recipients were required to be intubated after ten and 15 days, respectively. This kidney recipient was discharged in good health after 17 days. Thus, only the lung transplant recipient is on mechanical ventilation. Immunosuppression was adapted in five patients, but continued in all patients. Target trough levels were evaluated regularly and were within range during hospital stay. No graft loss or death was documented. Compared to non-transplanted patients the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 and LDH blood values. Conclusion: This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.

Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19.

BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N­terminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14 ng/l) in 47%, and a clinically relevant Troponin T elevation (10â€¯× URL) was found in three patients (6%). NT-proBNP was elevated (>300 pg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000 pg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17 mm and/or RV S' < 10 cm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.